The present invention, in some embodiments thereof, relates to peptide agents comprising anti-microbial properties and to methods of treating diseases using same.
Before the evolution of adaptive immunity in higher vertebrates added complexity, specificity, and memory to fight microbial challenge, a simpler, non-specific ancient system of innate immunity evolved 2.6 billion years ago and continues to function as the principal defense for almost all living organisms. Innate immunity is necessarily rapid, cidal, redundant, and multifunctional. The antimicrobial function of innate immunity is mediated, in part, by small cationic peptides with potent antimicrobial activity against Gram-positive and Gram-negative bacteria, fungi, parasites, and some viruses. The principal mechanism of rapid killing of microbial pathogens is attributed to perturbation of the microbial cell membrane, but present understanding is incomplete and other mechanisms may also be operative. Human antimicrobial peptides (AMPs) such as defensins and cathelicidin (LL-37) are present in leukocytes and are also secreted by various epithelia in skin and mucosal surfaces including the ocular surface. In addition to their antimicrobial role, AMPs also serve as important effector molecules in inflammation, immune activation, and wound healing.
The driving force for the development of newer anti-infectives is almost always the inevitable emergence of bacterial resistance to antibiotics following widespread clinical, veterinary, and animal agriculture (growth promoter in chickens, pigs, and feedlot cattle) usage. The pharmaceutical industry has continuously met this need by modifying existing antibiotics and developing newer antibiotics in a timely fashion. These successful efforts have produced the wide variety of currently available drug classes of antibiotics [beta lactams (penicillins, carbapenems, cepahalosporins), glycopeptides, macrolides, ketolides, aminoglycosides, fluoroquinolones, oxazolidinones, and others]. Similarly, there have been dramatic successes in developing effective antivirals to kill important clinical viral pathogens (e.g., HIV, herpes viruses, and influenza). However, the rapid emergence of resistance is even a greater problem for life-threatening viral infections. The best example remains HIV, where the rapid emergence of resistance to single drugs posed daunting clinical problems. The only effective solution to this problem was to develop combination therapy involving several antivirals with different mechanisms of inhibitory action. Currently, there are 19 different approved drugs for anti-HIV therapy in use as components of combination therapy. They include (1) nucleoside reverse transcriptase inhibitors, (2) nucleotide reverse transcriptase inhibitors, (3) non-nucleoside reverse transcriptase inhibitors, (4) proteases, and (5) viral entry blockers inhibitors.
Despite the success to date in antimicrobial development, the inexorable, ongoing emergence of resistance worldwide continues to spur the search for novel anti-infectives to replace and/or supplement conventional antibiotics.